A phase I/II, multicenter, randomized, double-blind, placebo within-patient controlled, first-in-human (FIH) Proof of Concept (PoC) study to evaluate the safety and efficacy of topically applied SXR1096 cream in patients with Netherton syndrome (NS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sixera Pharma AB

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

18 Feb 2022 → 9 Jun 2025

Decision date (initial)

2023-10-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2023-507743-11-00

EudraCT number

2021-003210-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective is to evaluate clinical safety and efficacy of the treatment with the IMP, compared to placebo, in patients with NS.

Secondary objectives 1

1. Secondary Objectives are: Part A) To assess the safety of SXR1096 multiple doses (7 days of treatment) in five adults Part B) To assess the safety and efficacy of 4 weeks treatment with SXR1096 in adults and adolescents (12-17 years)

Conditions and MedDRA coding

Netherton syndrome (NS)

Regulatory references

Scientific advice from competent authorities

Swedish Medical Products Agency

Plan to share IPD

No

IPD plan description

No plan to share IPD

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Male or female patients aged 18 to 65 years at the screening visit and also adolescents (12-17 years) only after initial cohort of 5 adult patients have been treated for at least 7 days (Part A). 2. Patients must be willing to provide written informed consent. Adolescents (as applicable in Part B) are eligible if all inclusion/exclusion criteria are met, benefits outweigh risks, are irreplaceable as a participant, and a legal guardian has conveyed and clarified the Informed Consent information to ascertain the subject’s understanding of it as adequate for the decision. 3. Clinical diagnosis of NS including at least 3 out of the 4 following clinical criteria; a. Neonatal erythroderma b. Bamboo hair and/or alopecia c. Chronic atopy specified as food allergy, asthma, rhino conjunctivitis and/or eczema for at least 2 years d. Ichthyosis linearis circumflexa 4. Patients must be willing and able to understand and can comply with study requirements, apply the medication as instructed and be able to complete the study. 5. Absent LEKTI on immunohistochemistry of skin biopsy and/or confirmed mutation in SPINK5 gene 6. NS involvement ≥ 20% of Body Surface Area (BSA) required at both the screening and baseline visits. 7. Investigator Global Assessment (IGA) of two areas to be treated, score ≥3, i.e. moderate or severe for each area required. Each target area approx. 9% of BSA. i.e. equal to one arm. 8. Female of childbearing potential must either commit true abstinence (as defined as refraining from heterosexual intercourse) during the complete trial when this is in line with the preferred and usual lifestyle of the subject, or use an adequate and approved highly effective method of contraception throughout the study and for 4 weeks after the last study drug application. This criterion also applies to a prepubertal female subject who begins menses during the study. Adequate and approved highly effective methods of contraception applicable for the subject and/or her partner are defined below: • Progestogen-only (oral, transdermal, injectable or implantable) hormonal contraception associated with inhibition of ovulation • Combined (oestrogen- and progestogen-containing) oral, , or transdermal hormonal contraception • Injectable or implanted hormonal contraception • Intrauterine devices or intrauterine hormone-releasing system • Bilateral tubal ligation or tube insert (such as the Essure system) at least 3 months before the study • Vasectomy of partner, confirmed to be the sole sexual partner, at least 3 months before the study with confirmed surgical success. • Female subjects of non-childbearing potential must meet one of the following criteria: • Absence of menstrual bleeding for 1 year prior to screening without any other medical reason • Documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy at least 3 months before screening • In adolescents who are not yet post-pubertal, eligibility demands the childbearing potential to have been evaluated by a suitably qualified medical practitioner and use of an acceptable sexual maturity rating scale (e.g. Tanner)

Exclusion criteria 1

1. 1. Female patient who is pregnant, nursing an infant or planning a pregnancy throughout the course of the study or is unwilling or unable to adhere to the contraception methods described herein 2. Patient with any uncontrolled systemic disease. A potential patient in whom therapy for a systemic disease is not yet stabile for at least 3 months will not be considered for entry into the study. 3. Patient with positive serology tests like HIV, HCV & HBsAg. 4. Patient with presence of any skin disease that might interfere with the diagnosis or evaluation of the test medications. Cutaneous infection within 1 week before the baseline visit or, any infection requiring treatment with oral or parenteral antibiotics, antivirals, antiparasitics, or antifungals within 2 weeks before the baseline visit. 5. Patient that has a condition or is in a situation, which in the investigator's opinion may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient's participation in the study. 6. Use of topical drugs that might alter the course of NS (e.g., topical corticosteroids and topical calcineurin inhibitors) within two weeks before baseline visit. 7. Patient with a known sensitivity to any of the study treatments and/or their components (detailed in Appendix E herein). 8. Patients with contact dermatitis-like reactions to the vehicle cream (placebo) evaluated at Screening (Appendix I) 9. Patient who anticipates a need to use other topical or systemic therapy that might alter the course of NS. Emollients/creams can be used on remaining skin area but not the test areas. Use of topical prescription treatment within 2 weeks prior to initial dosing of study drug. Recent systemic treatment for NS (e.g. systemic corticosteroids, antibiotics, immunosuppressant, biologic and biosimilars treatments). A washout period of 4 weeks will be required for such patients to be eligible to participate in the trial. 10. Patient who anticipates the need for surgery or hospitalization during the study. 11. Concurrent involvement in any other clinical study/expanded access program with an investigational drug or device, or participation in a clinical study within 30 days prior to entering the study. 12. Suspected or confirmed COVID-19 infection within 4 weeks before the screening or baseline visit. Unresolved COVID-19 infection. Planned vaccination for COVID-19 during screening, treatment period or before the follow-up visit.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • Primary endpoints: • Safety assessment includes adverse events (nature and incidence), physical examination, vital signs, laboratory safety, and local tolerability. • Primary efficacy endpoint: o The change in Investigator Global Assessment (IGA) score 0-4 (see table in Appendix B) at EOT compared to baseline.

Secondary endpoints 1

1. • Secondary efficacy endpoints: • The skin condition will be characterized primarily by Ichthyosis Area Severity Index (IASI), which integrates erythema (IASI-E) and scaling (IASI-S); this score has been recently developed and validated by applying it to patients affected with NS (Paller et al., 2017). • Skin itching will be assessed by VAS and a multidimensional 5-D pruritus scale (Phan et al., 2012). • Skin surface pH and transepidermal water loss (TEWL) will be measured on treated areas.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sixera Pharma AB

Sponsor organisation

Sixera Pharma AB

Address

Skeppsbron 16, Stockholms Domkyrkofors. Stockholms Domkyrkofors.

City

Stockholm

Postcode

111 30

Country

Sweden

Scientific contact point

Organisation

Sixera Pharma AB

Contact name

Maarten de Château

Public contact point

Organisation

Sixera Pharma AB

Contact name

Maarten de Château

Locations

4 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications